Divergent Effects of Joyful and Anxiety-Provoking Music on
Endothelial Vasoreactivity
MICHAEL MILLER, MD, C. CHARLES MANGANO, BA, RDMS, VALERIE BEACH, RN, WILLEM J. KOP, PHD,
AND ROBERT A. VOGEL, MD
Objective: To evaluate the extent to which music may affect endothelial function. In previous research, a link between music and
physiologic parameters such as heart rate and blood pressure has been observed. Methods: Randomized four-phase crossover and
counterbalanced trial in ten healthy, nonsmoking volunteers (70% male; mean age, 35.6 years) that included self-selections of music
evoking joy or provoking anxiety. Two additional phases included watching video clips to induce laughter and listening to audio
tapes to promote relaxation. To minimize emotional desensitization, subjects were asked to refrain from using self-selected tapes
and images for at least 2 weeks before the assigned study phase. Endothelial function was assessed by brachial artery flow-mediated
dilation (FMD) and measured as percent diameter change after an overnight fast. After baseline FMD measurements, subjects were
randomized to a 30-minute phase of the testing stimulus followed by poststudy FMD; they returned a minimum of 1 week later for
the subsequent task. A total of 160 FMD measurements were obtained. Results: Compared with baseline, music that evoked joy
was associated with increases in mean upper arm FMD (2.7% absolute increase; p ⬍ .001), whereas reductions in FMD were
observed after listening to music that elicited anxiety (0.6% absolute decrease; p ⫽ .005 difference between joyful and
anxiety-provoking music). Self-selected joyful music was associated with increased FMD to a magnitude previously observed with
aerobic activity or statin therapy. Conclusion: Listening to joyful music may be an adjunctive life-style intervention for the
promotion of vascular health. Key words: endothelial function, brachial artery reactivity testing, music, laughter.
FMD ⫽ flow-mediated dilation.
INTRODUCTION
sychosocial stress is associated with an increased risk of
coronary heart disease, which is partially related to stressinduced endothelial dysfunction (1). However, fewer studies
have evaluated the extent to which positive emotions may
affect the endothelium. We demonstrated that cinematic viewing of movie and television segments that evoked laughter was
associated with improved endothelial flow-mediated dilation
(FMD) as compared with video images inducing mental
stress (2). Because positive emotions, such as laughter, are
associated with release of natural opioid compounds (i.e.,
␤-endorphin) that up-regulate production of endotheliumderived nitric oxide (3), we hypothesized that other emotional stimuli may affect endothelial function.
Brachial artery reactivity testing has been used as a noninvasive surrogate of endothelial function. FMD is correlated
with the intracoronary vasomotor response post acetylcholine
administration (4,5), and reduced endothelial vasoreactivity
has been consistently identified in subjects with diabetes mellitus, hyperlipidemia, cigarette smoking, and hypertension (1).
Similar effects have also been observed in response to mental
stress or depression (6), raising the possibility that positive
emotions may exert an opposite effect on FMD. To this end,
we previously found that laughter improved FMD (2) and a
P
From the Division of Cardiology, University of Maryland Medical Center,
Baltimore, Maryland.
Address correspondence and reprint requests to Michael Miller, MD, Division of Cardiology, University of Maryland Medical Center, Baltimore, MD
21201. E-mail: mmiller@medicine.umaryland.edu
Received for publication September 9, 2009; revision received December
4, 2009.
Dr. Miller had full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the data
analysis.
This study was supported, in part, by Grant RO1HL61369 from the National Institutes of Health.
The authors have not disclosed any potential conflicts of interests.
DOI: 10.1097/PSY.0b013e3181da7968
354
0033-3174/10/7204-0354
Copyright © 2010 by the American Psychosomatic Society
recent study (7) reported improvement in arterial stiffness as
measured by pulse-wave velocity after induction of laughter.
The aim of the present study was to further evaluate positive
and negative stimuli and their potentially divergent effects on
FMD.
METHODS
Ten nonsmoking, normotensive, and normolipidemic men (n ⫽ 7) and
women (n ⫽ 3), aged 35.6 ⫾ 12.0 years, without a history of metabolic or
psychiatric disease were enrolled in this four-phased, randomized, counterbalanced, crossover study. The study was approved by the Institutional
Review Board at the University of Maryland Medical Center; all participants
provided their written informed consent. The study was conducted between
July 2006 and January 2007.
The four-phased study included 1) musical selections causing feelings of
joyfulness; 2) musical selections causing feelings of anxiety; 3) video segments causing laughter; and 4) audio tapes involving deep breathing and other
guided relaxation exercises. Musical and video choices were self-selected
based on a prior history of positive or negative emotional experiences to these
selections. For example, joyful musical selections were defined as having
created a sense of well-being or euphoria, whereas negative musical selections
were based on prior induction of anxiety. Similarly, examples of videos that
previously promoted laughter included clips from Saturday Night Live
(NBC), Shallow Hal (20th Century Fox, 2001), and others (2). Finally, the
audio tape used for the relaxation phase was guided by visual and auditory
imagery that volunteers had been exposed to before study entry. Each phase
was separated by a minimum of 1 week, and the volunteers were asked not to
listen to or watch the selections for a minimum of 2 weeks before testing.
On the morning of testing and after an overnight fast, endothelial-dependent FMD was assessed by brachial artery reactivity testing. Baseline FMD
images (pre and post occlusion) were acquired with the subject in a recumbent
position and temperature-controlled room (22°C) (4) for each of the four
phases. Subsequently, volunteers listened to or viewed selections for 30
minutes after which poststimulus FMD images (pre and post occlusion) were
acquired. Brachial artery images were obtained, using an 11-MHz to 5-MHz
broadband linear-array transducer. One dedicated research ultrasonographer
performed all (baseline and post stimulus) studies. Images were acquired 1
minute ⫾ 15 seconds after releasing the blood pressure cuff after 5 minutes
of upper-arm occlusion. For each phase, a total of four FMD images (pre and
post occlusion at baseline and after study stimuli) were collected. Therefore,
each volunteer underwent 16 FMD images for a total of 160 arterial measurements during the study. FMD was quantified as percent diameter difference between baseline and post occlusion arterial diameter; end-diastolic
Psychosomatic Medicine 72:354 –356 (2010)
MUSIC AND ENDOTHELIAL VASOREACTIVITY
frames were analyzed by a single investigator who was blinded to the identity
and study phase.
Data are presented as mean ⫾ standard error of the mean or percentages
as appropriate. Study phase-induced responses in FMD were examined, using
a 2 ⫻ 4 repeated-measures analyses of variance with two within-subject
factors: a) study phase response (baseline versus phase); and b) type of study
phase (joyful music, anxiety-provoking music, relaxation, and laughter). A
significant “response ⫻ type of phase” interaction was used as indicator of
differential responses to the study phases. Post hoc paired t tests were used to
examine responses to each of the four phases individually. A p ⬍ .05 was
considered statistically significant.
RESULTS
Results for baseline and study phase-induced FMD are
presented in Table 1. Analysis of variance indicated that
responses differed significantly across the four positive provocation phases (Finteraction(3,7)) ⫽ 4.64, p ⫽ .043 and a
marginally significant main effect for response from baseline
to study phase (F(1,9) ⫽ 4.28, p ⫽ .068). Analyses per phase
revealed significant vasodilation in response to the joyful
music (p ⬍ .001) and a marginally significant response to
laughter (p ⫽ .08), whereas responses to anxiety-provoking
music (p ⫽ .37) and relaxation (p ⫽ .46) were nonsignificant.
Figure 1 illustrates individual FMD responses at baseline
and after listening to joyful or anxiety-provoking music for 30
minutes. Nine of ten volunteers experienced increased FMD
TABLE 1. Mean (ⴞStandard Error) Percent Change in Brachial
Artery Flow-Mediated Vasodilation at Baseline and After Each
Study Phase
Joyful music
Laughter
Anxious music
Relaxation
Figure 1.
Baseline
Post
p
10.12 (1.42)
10.68 (1.63)
10.65 (1.39)
10.58 (1.16)
12.78 (1.46)
12.73 (1.40)
10.04 (1.44)
11.72 (1.66)
⬍.001
.08
.37
.46
(2.7% absolute increase; p ⬍ .001) after listening to joyful
music. The mean FMD after listening to joyful music was significantly larger than the FMD response to anxiety-provoking
music (p ⫽ .005). The pattern of results was not confounded by
drift in the pre task baseline FMD (p ⫽ .88), and mean
baseline diameters before each of the four phases (pre laughter, 3.28 ⫾ 0.70 mm [range, 2.50 – 4.46]; prejoyful music,
3.34 ⫾ 0.70 mm [range, 2.47– 4.56]; pre anxious music,
3.24 ⫾ 0.64 mm [range, 2.47– 4.24]; pre relaxation, 3.21 ⫾
0.64 mm [range, 2.50 – 4.37]), suggesting internal technical
consistency in image acquisition and subject compliance with
protocol requirements.
DISCUSSION
The present study shows that music results in improved
endothelial function as measured by flow-mediated vasodilation. In addition to the autonomic variables induced by rhythm
and tempo effects (8), we found that musical compositions that
were self-selected on the basis of being joyful or anxiety-provoking support a physiologic role for music that is broadened beyond
effects previously observed on blood pressure and heart rate (9).
Although the mechanism(s) underlying the effect of positive
emotions on endothelial vasoreactivity remains to be elucidated,
one possible link is ␤-endorphin-mediated activation of endothelium-derived nitric oxide, an effect opposite to that observed in
response to mental stress when the potent vasoconstrictor endothelin-1 is released (10). Other biomarkers associated with music
listening include oxytocin secretion (11).
There are potential limitations associated with the study.
First, brachial artery diameter was measured at 1 minute ⫾ 15
seconds after release of cuff pressure, and this interval may
have been too short to capture the maximum rate of dilation in
some individuals due to interindividual variability. However,
because each subject served as his/her control for all four
study phases, the absence of maximal dilation would have
Brachial artery flow-mediated dilation at baseline and after listening to joyful or anxiety-provoking music for 30 minutes.
Psychosomatic Medicine 72:354 –356 (2010)
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M. MILLER et al.
been expected to occur consistently after each of the randomized phases. Nevertheless, this potential shortcoming can be
overcome in future studies, using modern software that precisely captures peak FMD. In addition, although we did not
specifically address the potential painful effects of brachial
artery occlusion for 5 minutes, it is plausible that an abnormal
endothelial response to this iatrogenic stressor may have been
attenuated after listening to joyful music (12).
In summary, the ⬎2.5% absolute change in FMD observed
between joyful and anxiety-provoking music is suggestive of
meaningful differences between the conditions (13) and raises
the possibility that positive emotions beneficially affect vascular health. However, the clinical implications of these effects require further study.
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